Since the early events in antigen activation occur at the level of the cell membrane, the effect of aging on membrane receptors and function will be investigated. Splenic cells from young and old mice were separated into subpopulations by their differences in density, adherence to nylon wool, and differential susceptibility to antisera reagents. The subpopulations were viewed with scanning electron microscopy following each treatment. The lymphoid cells of old mice are more fragile under conditions where antisera is employed than are the cells from young mice. A new tri-labelling technique was developed which permits unambiguous identification of subpopulations of cells and quantitation of distinct cell surface receptors on individual cells as well as permitting kinetic studies of the membrane changes following the binding of a liquid with its receptor.